Variant 4-121380426-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_198179.3(QRFPR):c.222G>T(p.Lys74Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

QRFPR
NM_198179.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.326

Variant links:

Genes affected

QRFPR (HGNC:15565): (pyroglutamylated RFamide peptide receptor) Enables G protein-coupled receptor activity. Involved in G protein-coupled receptor signaling pathway. Predicted to be located in non-motile cilium. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

QRFPR links:

QRFPR (HGNC:):

QRFPR links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40298218).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QRFPR	NM_198179.3 linkuse as main transcript	c.222G>T	p.Lys74Asn	missense_variant	1/6	ENST00000394427.3	NP_937822.2	Q96P65
QRFPR	XM_017008693.3 linkuse as main transcript	c.222G>T	p.Lys74Asn	missense_variant	1/4		XP_016864182.1	F2Z3L3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
QRFPR	ENST00000394427.3 linkuse as main transcript	c.222G>T	p.Lys74Asn	missense_variant	1/6	1	NM_198179.3	ENSP00000377948.2	Q96P65
QRFPR	ENST00000512235.1 linkuse as main transcript	n.634G>T		non_coding_transcript_exon_variant	1/2	1
QRFPR	ENST00000334383.9 linkuse as main transcript	c.222G>T	p.Lys74Asn	missense_variant	1/6	2		ENSP00000335610.5	J3KNR3
QRFPR	ENST00000507331.5 linkuse as main transcript	n.222G>T		non_coding_transcript_exon_variant	1/7	2		ENSP00000423369.1	F2Z3L3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251428

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2022

The c.222G>T (p.K74N) alteration is located in exon 1 (coding exon 1) of the QRFPR gene. This alteration results from a G to T substitution at nucleotide position 222, causing the lysine (K) at amino acid position 74 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

.;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.52

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Pathogenic

3.1

.;M

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-4.2

D;D

REVEL

Benign

0.25

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.99

.;D

Vest4

0.28

MutPred

0.63

Loss of methylation at K74 (P = 0.0112);Loss of methylation at K74 (P = 0.0112);

MVP

0.73

MPC

1.4

ClinPred

0.97

GERP RS

4.3

Varity_R

0.83

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over